Structural and Psychosocial Syndemic Conditions and Condomless Anal Intercourse Among Transgender Women — National HIV Behavioral Surveillance Among Transgender Women, Seven Urban Areas, United States, 2019–2020

Psychosocial and structural syndemic conditions, including polydrug use and experiencing homelessness, frequently co-occur and might jointly increase HIV risk. Limited studies have assessed racial and ethnic differences in exposure to syndemic conditions and behaviors associated with HIV transmission among transgender women. This report examines the relation between syndemic conditions and condomless anal intercourse (CAI) among transgender women in seven urban areas in the United States to develop HIV prevention interventions for transgender women. During 2019–2020, transgender women in seven urban areas were recruited using respondent-driven sampling for a biobehavioral survey. Reported syndemic conditions (psychosocial: polydrug use, sexual violence, and psychological distress; structural: homelessness, incarceration, and exchange sex) were summed to create a syndemic score. Using modified Poisson regression to account for RDS, the study assessed whether the strength of the association between syndemic score and CAI differed by race and ethnicity. To assess additive interaction, the relative excess prevalence owing to interaction (REPI) and 95% CIs for selected pairs of syndemic conditions on CAI prevalence stratified by race and ethnicity were estimated. Of 1,348 transgender women (Black = 546, White = 176, and Hispanic = 626), 55% reported CAI; and 24% reported ≥3 syndemic conditions. Reporting additional syndemic conditions was associated with CAI for White, Hispanic, and Black participants. The association was significantly stronger for White than Black and Hispanic participants. Limited significant superadditive interactions were found, although the majority were between structural syndemic conditions. Racial and ethnic differences in REPI estimates were observed. Reporting more syndemic conditions was associated with increased CAI across racial and ethnic groups, demonstrating that HIV prevention efforts for transgender women should address structural and psychosocial syndemic conditions. Results differed by race and ethnicity, indicating that syndemic-focused interventions for transgender women should be tailored to racial and ethnic groups.


Introduction
Transgender women are disproportionately affected by HIV, and severe racial and ethnic disparities in HIV prevalence among transgender women exist (1,2).Transgender women might be disproportionately affected by HIV because they experience high levels of social, legal, and economic marginalization, thereby increasing exposure to syndemic conditions, including experiencing homelessness, incarceration, exchange sex, polydrug use, violence, and psychological distress (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13).Syndemic theory posits that epidemics are produced by both diseases and social conditions (14,15).The theory emphasizes how structural factors (e.g., experiencing homelessness and incarceration) and psychosocial factors (e.g., sexual violence and polydrug use) jointly increase risk for HIV acquisition and transmission (14,15).Differences in exposure to syndemic conditions by race and ethnicity might explain the racial and ethnic disparities in HIV prevalence (7).No studies have assessed racial and ethnic disparities in syndemic conditions and behaviors associated with HIV transmission in a population-based sample of transgender women (16).
This report examines the relation between structural and psychosocial syndemic conditions (experiencing homelessness, incarceration, exchange sex, polydrug use, sexual violence, and psychological distress) and condomless anal intercourse (CAI) among Black or African American (Black), White, and Hispanic or Latina (Hispanic), transgender women in the United States.(Persons of Hispanic origin might be of

Measures
The outcome variable was past-year CAI, which was defined as having insertive or receptive anal sex without a condom during the past 12 months (Table 1).Psychosocial syndemic conditions included past-year polydrug use, past-year experience of sexual violence, and past-month psychological distress.Polydrug use was defined as having used speedball (combination of heroin and cocaine) or two or more types of drugs via injection or noninjection that were not provided by a health care professional during the past 12 months, including heroin, powder cocaine, crack cocaine, methamphetamine, painkillers (e.g., Oxycontin, Vicodin, morphine, or Percocet), downers (e.g., Klonopin, Valium, Ativan, or Xanax), or poppers or amyl nitrate; marijuana, alcohol, and fentanyl were not included.Experience of sexual violence was defined as being physically forced or verbally threatened to have sex when they did not want to during the past 12 months.To measure psychological distress, participants completed the validated, widely-used Kessler Psychological Distress Scale comprising six items asking participants how often they have been feeling emotions (e.g., nervous or hopeless) during the past 30 days; response options ranged from "All of the time" to "None of the time" (18)(19)(20).Participants with a composite score of 13-24 were categorized as experiencing psychological distress; those with a score of <13 were categorized as not experiencing psychological distress (18,19).
Structural syndemic conditions included past-year experiencing homelessness, past-year incarceration, and pastyear exchange sex.Experiencing homelessness was defined as living on the street, in a shelter, in a single-room occupancy hotel, or in a car at any time during the past 12 months.Incarceration was defined as being held in a detention center, jail, or prison for >24 hours during the past 12 months.Exchange sex was defined as ever having received money or drugs in exchange for sex during the past 12 months.A syndemic score was calculated by summing together the number of structural and psychosocial syndemic conditions reported by each participant (range = 0-6).Covariates (age group, education level, relationship status, health insurance, and NHBS HIV test result) were selected based on their potential to confound the relation between syndemic conditions and CAI (4,5,13,21).

Data Analysis
This analysis was conducted in four steps using SAS software (version 9.4; SAS Institute).First, descriptive analyses were used to characterize the overall sample and by racial and ethnic groups.Second, the independent associations between syndemic conditions and between each syndemic condition and CAI were estimated and stratified by race and ethnicity.Modified Poisson regression was used to generate adjusted prevalence ratios and 95% CIs for associations between pairs of syndemic conditions and between each syndemic condition and CAI.Third, analyses were conducted to assess whether the strength of the association between syndemic score and CAI differed by race and ethnicity (Figure 1).The effect of syndemic score, race and ethnicity, and interactions among syndemic score and race and ethnicity on CAI were estimated.For significant interaction terms (p<0.05), the effect of the syndemic score on the predicted probability of CAI by racial and ethnic group was estimated and graphed to visualize the relations.Nonsignificant interaction terms were removed from the model.Finally, additive interactions between syndemic conditions on CAI were assessed and stratified by race and ethnicity.The relative excess prevalence owing to interaction (REPI) and 95% CIs were estimated for selected pairs of syndemic conditions (22)(23)(24)(25)(26)(27).Pairs of syndemic conditions were selected based on empirical evidence of potential interactions on CAI among transgender women (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)28,29).REPI is one of the measures of additive interaction, or the difference of prevalence differences, as a proportion of baseline prevalence (22,24,30).A statistically significant REPI >0 indicates superadditivity and a statistically significant REPI <0 indicates subadditivity (22,24).Superadditivity indicates that two syndemic conditions produced a larger than expected prevalence of CAI beyond the sum of the independent effects of the conditions (22,24).Subadditivity indicates that the effects of two syndemic conditions on CAI was lower than the sum of the independent effects of the conditions (22,30).The regression analyses were conducted using modified Poisson regression with robust error variance (31) and accounted for respondent-driven sampling method by clustering on recruitment chain and adjusting for urban area and network size.Analyses also controlled for covariates (age group, education level, relationship status, health insurance, and NHBS HIV test result).

Results
The sample comprised 1,348 transgender women (Black = 546, White = 176, and Hispanic = 626) (Table 2).Most participants were aged ≥30 years (68.9%).Nearly half of participants received an HIV-positive test result (43.5%); higher percentages of Black (61.7%) and Hispanic (  Abbreviations: CAI = condomless anal intercourse; NHBS = National HIV Behavioral Surveillance.* N = 1,348 participants had an HIV-negative or HIV-positive NHBS HIV test result; identified as Black or African American, White, or Hispanic or Latina; and had no missing outcome data.† Atlanta, GA; Los Angeles, CA; New Orleans, LA; New York City, NY; Philadelphia, PA; San Francisco, CA; and Seattle, WA. § Persons of Hispanic or Latina (Hispanic) origin might be of any race but are categorized as Hispanic; all racial groups are non-Hispanic.¶ Missing: Age: n = 1; education: n = 2; relationship status: n = 21; polydrug use: n = 5; sexual violence: n = 5; psychological distress: n = 4; homelessness: n = 2; incarceration: n = 3; and syndemic score: n = 17.** Being partnered was defined as having at least one main sexual partner during the past 12 months.A main sexual partner was defined as someone the participant felt committed to above anyone else (e.g., a boyfriend, girlfriend, significant other, or life partner).† † Participants with a reactive rapid NHBS HIV test result confirmed by supplemental rapid or laboratory-based HIV testing were categorized as HIV positive.
Participants who self-reported being HIV negative and had a nonreactive rapid NHBS HIV test result were categorized as HIV negative.§ § Polydrug use was defined as having used speedball (combination of heroin and cocaine) or two or more of the following types of drugs via injection or noninjection during the past 12 months: heroin; powder cocaine; crack cocaine; methamphetamine; painkillers (e.g., Oxycontin, Vicodin, morphine, or Percocet); downers (e.g., Klonopin, Valium, Ativan, or Xanax); or poppers or amyl nitrate.¶ ¶ Sexual violence was defined as having been physically forced or verbally threatened to have sex when they did not want to.*** Participants with a composite score of 13-24 were categorized as experiencing psychological distress; those with a score <13 were categorized as not experiencing psychological distress.† † † Exchange sex was defined as having received money or drugs in exchange for sex.§ § § Experiencing homelessness was defined as living on the street, in a shelter, in a single room occupancy hotel, or in a car.¶ ¶ ¶ Incarceration was defined as being held in a detention center, jail, or prison for >24 hours.**** An overall syndemic score (0-6) for each participant was calculated by summing reported syndemic conditions (e.g., homelessness, incarceration, exchange sex, polydrug use, sexual violence, and psychological distress).† † † † Condomless anal intercourse was defined as having insertive or receptive anal sex without a condom.percent of participants reported three or more syndemic conditions, including 30.8% of White participants, 23.1% of Black participants, and 23.0% of Hispanic participants.Among all participants, 54.9% reported CAI (57.8% of Hispanic participants, 52.7% of Black participants, and 51.1% of White participants).

Independent Associations Between Syndemic Conditions and Between Syndemic Conditions and CAI
Positive associations between most pairs of syndemic conditions were observed across racial and ethnic groups (Table 3).However, observed associations between syndemic conditions and CAI differed by race and ethnicity.Among Black participants, only exchange sex and polydrug use were independently associated with CAI.For White and Hispanic participants, all associations between syndemic conditions and CAI were significant except for the relation between psychological distress and CAI.

Association Between Syndemic Score and CAI
Reporting more syndemic conditions was significantly associated with reporting CAI for White, Hispanic, and Black participants (Table 4).Both interaction terms for syndemic score by race and ethnicity were statistically significant, illustrating that the association between syndemic score and CAI was significantly stronger for White than Hispanic and Black participants (Table 4) (Figure 2).

Discussion
In this analysis, syndemic conditions and CAI were prevalent among transgender women.Independent associations between syndemic conditions and between syndemic conditions and CAI were observed, demonstrating that HIV prevention efforts for transgender women should address structural and psychosocial syndemic conditions (10,11,32).Further, reporting more syndemic conditions was associated with increased CAI prevalence across racial and ethnic groups.Findings are consistent with other studies examining relations between co-occurring syndemic conditions and behaviors associated with HIV transmission among transgender women (3)(4)(5)(6).
This analysis adds to the literature by testing for additive interactions between selected combinations of structural and psychosocial syndemic conditions on CAI.Similar analytic approaches have been used in research with men who have sex with men and help identify specific combinations of syndemic conditions that result in increased likelihood of behaviors associated with HIV transmission and help develop tailored intervention responses (25,27,33,34).In this analysis, limited significant superadditive interactions were found, although the majority were between structural syndemic conditions (e.g., superadditive interactions between experiencing homelessness and exchange sex on CAI prevalence among Black and White participants).These results underscore the importance of prioritizing HIV prevention interventions that address social determinants of health (e.g., housing and poverty) (32,35).Notably, the same combinations of syndemic conditions often resulted in a superadditive interaction for one racial and ethnic group and a subadditive interaction for another Abbreviation: aPR = adjusted prevalence ratio.* N = 1,309 participants had an HIV-negative or HIV-positive National HIV Behavioral Surveillance HIV test result; identified as Black or African American, White, or Hispanic or Latina (Hispanic); and had no missing data.† Models account for respondent-driven sampling method by clustering on recruitment chain and adjusting for urban area and network size.Models also control for age, education level, relationship status, health insurance, and National HIV Behavioral Surveillance HIV test result.§ Atlanta, GA; Los Angeles, CA; New Orleans, LA; New York City, NY; Philadelphia, PA; San Francisco, CA; and Seattle, WA. ¶ Dashes indicate no results available.** aPR statistically significant at p<0.05.
† † Persons of Hispanic origin might be of any race but are categorized as Hispanic; all racial groups are non-Hispanic.§ § Models did not control for urban area because models did not converge.
racial and ethnic group.For example, a subadditive interaction between sexual violence and psychological distress was found among Hispanic participants, and a superadditive interaction was found among White participants.These differences in interaction results demonstrate the need to tailor syndemic interventions to racial and ethnic groups.Additional research is also needed to explore why interactions might differ across racial and ethnic groups.
Prevalence estimates for syndemic conditions differed by race and ethnicity.Psychosocial syndemic conditions were reported most frequently by White participants, which might be explained in multiple ways.First, polydrug use might be higher among White participants because the opioid epidemic disproportionately affects White persons (36).More research is needed to improve understanding of racial and ethnic differences in substance use among transgender women (37).Second, John Henryism might explain the lower levels of reported psychological distress among Black participants (38,39).John Henryism is a high-effort, active coping style often used by Black persons to deal with psychosocial and environmental stressors (38,39).Studies have found associations between John Henryism and increased physical health problems (e.g., hypertension) among Black residents of the United States, especially Black men (38,40).Certain studies have also found that John Henryism is associated with reduced reporting of mental health problems, although additional research is needed (41)(42)(43).Alternatively, another mental health measure (e.g., depressive symptoms) might better capture mental health problems affecting this population than does psychological distress.Other studies have had mixed results and found Black gender minority participants are at lower or equal risk for depression compared with White gender minority participants (44,45).
Racial and ethnic differences also were observed in reported structural syndemic conditions.Black and Hispanic participants reported higher levels of exchange sex and incarceration than White participants.The higher prevalence of exchange sex might be a result of more severe economic marginalization because of racial and ethnic discrimination (13), and the higher prevalence of incarceration is likely because of the disproportionate impact of mass incarceration on Black and Hispanic populations (46,47).However, structural and psychosocial syndemic conditions were prevalent across racial and ethnic groups, underscoring the importance of addressing syndemic conditions for all transgender women.
Findings differed by racial and ethnic group, highlighting the importance of assessing racial and ethnic differences in HIV prevention research among transgender women (48).Syndemic theory emphasizes that disparities in health outcomes or interactions between health outcomes are produced by social Predicted probability

Syndemic score
Black or African American White Hispanic or Latina * Persons of Hispanic or Latina (Hispanic) origin might be of any race but are categorized as Hispanic; all racial groups are non-Hispanic.† N = 1,309 participants had an HIV-negative or HIV-positive National HIV Behavioral Surveillance HIV test result; identified as Black or African American, White, or Hispanic or Latina; and had no missing data.§ Atlanta, GA; Los Angeles, CA; New Orleans, LA, New York City, NY; Philadelphia, PA; San Francisco, CA, and Seattle, WA.
or environmental factors (14,15).Future syndemics research should consider including racial and ethnic discrimination measures and apply an intersectional framework to improve understanding on how social and environmental factors produce racial and ethnic disparities in syndemic conditions and behaviors associated with HIV transmission among transgender women (44,(49)(50)(51)(52).In addition, testing protective factors (e.g., resilience and social support) as effect modifiers might help explain racial and ethnic differences in associations between syndemic conditions and behaviors associated with HIV transmission (6).

Limitations
General limitations for NHBS-Trans are available in the overview and methodology report of this supplement (17).The findings in this report are subject to at least six additional limitations.First, temporality between syndemic conditions and between the syndemic conditions and CAI could not be assessed because of the cross-sectional study design and overlapping recall periods for measures.Nevertheless, both structural and psychosocial syndemic conditions were included in the analysis, which allowed for testing of * Models account for respondent-driven sampling methodology by clustering on recruitment chain and adjusting for urban area.Models also control for age, education level, relationship status, health insurance, and National HIV Behavioral Surveillance test result.† An REPI estimate >0 indicates superadditivity between syndemic conditions on CAI.A REPI estimate <0 indicates subadditivity effects between syndemic conditions on CAI.§ Persons of Hispanic or Latina (Hispanic) origin might be of any race but are categorized as Hispanic; all racial groups are non-Hispanic.¶ Atlanta, GA; Los Angeles, CA; New Orleans, LA, New York City, NY; Philadelphia, PA; San Francisco, CA, and Seattle, WA. ** REPI estimates with a 95% CI that does not include zero are marked with a triangle (∆).
† † N = 1,309 participants had an HIV-negative or HIV-positive National HIV Behavioral Surveillance HIV test result; identified as Black or African American, White, or Hispanic or Latina; and had no missing data.additive interactions between structural syndemic conditions, psychosocial syndemic conditions, and structural and psychosocial syndemic conditions on CAI prevalence.Second, the sample is not representative of transgender women residing outside of the seven urban areas.Because transgender women are hard to reach, the data might not be representative of all transgender women residing in the seven urban areas.However, data were collected from multiple diverse urban areas using a robust, standardized surveillance system (2).Third, the sample size differed by racial and ethnic group and was most limited among White participants, which likely influenced the precision of parameter estimates and might have reduced power to detect associations.Nonetheless, Black and Hispanic populations disproportionately affected by HIV were over sampled, allowing for a stratified analysis to examine racial and ethnic differences in associations between syndemic conditions and CAI (2).Fourth, participants may have been at low or minimal risk of acquiring or transmitting HIV through CAI if they were taking preexposure prophylaxis or HIV treatment medication as prescribed; we were not able to determine if participants with HIV had an undetectable viral load or participants without HIV had full protection from taking preexposure prophylaxis every time they had CAI.Fifth, multiple comparisons were not adjusted, increasing the likelihood of type I errors when assessing independent associations between syndemic conditions and between syndemic conditions and CAI.Finally, all measures except for NHBS HIV test result were self-reported, which might be subject to social desirability bias and result in underreporting of syndemic conditions and CAI (53)(54)(55).

Conclusions
Because of the high prevalence of syndemic conditions and CAI, culturally sensitive HIV prevention and behavioral, biomedical, and structural interventions for transgender women are urgently needed (10,11,32).HIV behavioral interventions addressing risks associated with certain sexual behaviors, mental health symptoms, and substance use for transgender women have reduced behaviors associated with HIV transmission (56)(57)(58)(59)(60).Although limited, behavioral interventions designed to address psychosocial and structural syndemic conditions (e.g., homelessness, legal employment and income, and mental health symptoms among transgender women) also have indicated promising reductions in behaviors associated with HIV transmission (35,(61)(62)(63).Findings indicated differences in prevalence of syndemic conditions and interactions between syndemic conditions on CAI by racial and ethnic group, suggesting that syndemic-focused interventions for transgender women should be tailored to racial and ethnic groups.Results indicate that syndemic-focused interventions for Black transgender women should address the intersection between experiencing homelessness and exchange sex; those for Hispanic transgender women should address the intersection between exchange sex and polydrug use; and those for White transgender women should address the intersections between sexual violence and psychological distress, incarceration and experiencing homelessness, and experiencing homelessness and exchange sex.Culturally tailored syndemic-focused interventions that offer comprehensive services addressing social and structural barriers to status-neutral HIV services might be effective (64,65).For example, interventions designed for transgender women of color with HIV infection have increased engagement in HIV care by offering patient navigation or case management, housing and employment assistance, mental health services, and substance use services (65).Although HIV behavioral interventions have proven efficacy among transgender women, multilevel interventions are also critical to reduce gender-identity-related and racialand ethnic-related stigma and discrimination and increase access to pre-exposure prophylaxis, HIV treatment, and gender-affirming medical care (32,66).

FIGURE 2 .
FIGURE 2. Estimated condomless anal intercourse as a function of syndemic score and race and ethnicity* for Black or African American, White, and Hispanic or Latina transgender women † -National HIV Behavioral Surveillance Among Transgender Women, seven urban areas, § United States, 2019-2020

TABLE 1 . Variables, questions, and analytic coding for selected sociodemographic characteristics, syndemic conditions, and occurrence of condomless anal intercourse among transgender women -National HIV Behavioral Surveillance System Among Transgender Women, seven urban areas,* United States, 2019-2020
† Determined based on NHBS HIV test results.§ Persons of Hispanic or Latina (Hispanic) origin might be of any race but are categorized as Hispanic; all racial groups are non-Hispanic.¶ Determined based on study project area location.FIGURE 1.

Conceptual model of analysis showing factors contributing to condomless anal intercourse -National HIV Behavioral Surveillance Among Transgender Women, seven urban areas,* United States, 2019-2020
* Atlanta, GA; Los Angeles, CA; New Orleans, LA; New York City, NY; Philadelphia, PA; San Francisco, CA; and Seattle, WA.